Enantiocontrolled Cyclization to Form Chiral 7- and 8-Membered Rings Unified by the Same Catalyst Operating with Different Mechanisms.

Chiral medium-sized rings, albeit displaying attractive properties for drug development, suffer from numerous synthetic challenges due to difficult cyclization steps that must take place to form these unusually strained, atropisomeric rings from sterically crowded precursors. In fact, catalytic enantioselective cyclization methods for the formation of chiral seven-membered rings are unknown, and the corresponding eight-membered variants are also sparse. In this work, we present a substrate preorganization-based, enantioselective, organocatalytic strategy to construct seven- and eight-membered rings featuring chirality that is intrinsic to the ring in the absence of singular stereogenic atoms or single bond axes of chirality.

Suggested Dosing of Select Beta-lactam Agents for the Treatment of Antimicrobial-Resistant Gram-Negative Infections in Children.

Background: The Infectious Diseases Society of America (IDSA) publishes annual guidance on the treatment of antimicrobial-resistant (AMR) gram-negative infections. Within the AMR guidance, suggested dosages of antibiotics for adults infected with AMR pathogens are provided. This document serves as a companion document to the IDSA guidance to assist pediatric specialists with dosing β-lactam agents for the treatment of AMR infections in children.

The History and Advancement of Light, Lasers, and Energy-Based Devices in Dermatologic Surgery.

Background: From the theoretical foundations of laser and energy-based applications for the skin to the development of advanced medical devices, the field of dermatologic surgery has undergone transformative changes.

Objective: To review the scientific and clinical advancement of laser and energy-based therapies within dermatologic surgery.

Materials And Methods: A literature search was conducted to identify important scientific advancements and landmark studies on light, laser, and energy-based devices within the field of dermatologic surgery.

GLP-1RA Use and Thyroid Cancer Risk.

Importance: The increasing use of glucagon-like peptide-1 receptor agonists (GLP-1RA) demands a better understanding of their association with thyroid cancer.

Objective: To estimate the risk of incident thyroid cancer among adults with type 2 diabetes being treated with GLP-1RA vs other common glucose-lowering medications.

Design, Setting, And Participants: This was a prespecified secondary analysis of a target trial emulation of a comparative effectiveness study using claims data for enrollees in commercial, Medicare Advantage, and Medicare fee-for-service plans across the US.

Stakeholder Perceptions of Digital Nutrition Education Modules on Infant Feeding in Home Visiting Programs.

Objective: Evaluate the usability and acceptability of a digital infant feeding module for use in a home visiting program.

Methods: Home visitors (n = 11) and mothers (n = 10) completed a qualitative interview while viewing a digital nutrition education module on infant feeding. Quantitative data were collected using the mHealth App Usability Questionnaire.

A Stereoselective Oxidative Dimerization En Route to (-)-Lomaiviticin A.

We describe a stereoselective synthesis of the dimeric diazofluorene , a potential precursor to the cytotoxic -symmetric bacterial metabolite (-)-lomaiviticin A (). An efficient route was developed to convert the tetracyclic diol to the diketone (five steps, 30% overall). Oxidative dimerization of the enoxysilane provided the -symmetric dimeric diazofluorene in 56% yield and with 15:1:0 diastereoselectivity.

[2Fe-2S] model compounds.

This feature article reviews the synthesis, structural comparison, and physical properties of [2Fe-2S] model compounds, which serve as vital tools for understanding the structure and function of Fe-S clusters in biological systems. We explore various synthetic methods for constructing [2Fe-2S] cores, offering insights into their biomimetic relevance. A comprehensive analysis and comparison of Mössbauer spectroscopy data between model compounds and natural protein systems are provided, highlighting the structural and electronic parallels.

Long-term safety and efficacy of ritlecitinib in adults and adolescents with alopecia areata and at least 25% scalp hair loss: Results from the ALLEGRO-LT phase 3, open-label study.

Background: ALLEGRO-LT is an ongoing, long-term, open-label, multicentre, phase 3 study of ritlecitinib in adults and adolescents with alopecia areata (AA).

Objectives: To evaluate ritlecitinib safety and efficacy through Month 24 in patients with AA and ≥25% scalp hair loss.

Methods: ALLEGRO-LT enrolled rollover patients who previously received study intervention in either ALLEGRO phase 2a or 2b/3 studies and de novo patients who had not received treatment in either study.

A Commensurate Prior Model With Random Effects for Survival and Competing Risk Outcomes to Accommodate Historical Controls.

Clinical trials (CTs) often suffer from small sample sizes due to limited budgets and patient enrollment challenges. Using historical data for the CT data analysis may boost statistical power and reduce the required sample size. Existing methods on borrowing information from historical data with right-censored outcomes did not consider matching between historical data and CT data to reduce the heterogeneity.

Corrigendum: Combining Charlson comorbidity and VACS indices improves prognostic accuracy for all-cause mortality for patients with and without HIV in the Veterans Health Administration.

[This corrects the article DOI: 10.3389/fmed.2023.

Low-Cost Lower Extremity Screening to Predict Shoulder Distraction Force in College Softball Pitchers.

Background: During a windmill softball pitch, the throwing shoulder experiences forces greater than the pitcher's body weight. Various kinematic, kinetic, and performance factors have been related to shoulder forces and torques in softball pitchers, and softball research has examined clinical screening measures such as range of motion, muscular strength, and/or neuromuscular control. However, no studies have explicitly identified low-cost, clinic-friendly screening measures predictive of shoulder distraction forces in softball pitchers.

Putting seedlings on the map: Trade-offs in demographic rates between ontogenetic size classes in five tropical forests.

All species must partition resources among the processes that underly growth, survival, and reproduction. The resulting demographic trade-offs constrain the range of viable life-history strategies and are hypothesized to promote local coexistence. Tropical forests pose ideal systems to study demographic trade-offs as they have a high diversity of coexisting tree species whose life-history strategies tend to align along two orthogonal axes of variation: a growth-survival trade-off that separates species with fast growth from species with high survival and a stature-recruitment trade-off that separates species that achieve large stature from species with high recruitment.

Operating Characteristics of the Simulated Healthy Participant Approach in Impaired Clearance Studies.

Minimizing harm is a cornerstone of ethical research practices. A drug that has undergone extensive clinical pharmacological testing in healthy participants (HPs) and a diverse selection of patients can be described with a sufficiently predictive population pharmacokinetic (PopPK) model. In impaired clearance trials, recruitment is minimized and underpowered for all but major exposure differences.

Regulation of erm(T) MLS phenotype expression in the emergent emm92 type group A Streptococcus.

In the last decade, invasive group A Streptococcus (iGAS) infections have doubled in the US, with equivalent increases in MLS (macrolide, lincosamide, and streptogramin B)-resistance. The emm92-type isolates carrying the erm(T) gene have been associated with an alarming emergence of iGAS infections in people who inject drugs or experience homelessness. Our goal was to elucidate the mechanisms behind inducible (iMLS) and constitutive (cMLS) resistance in emm92 isolates.

The PRO-AGE Tool and Its Association With Post Discharge Outcomes in Older Adults Admitted From the Emergency Department.

Background: Existing risk scores assessing geriatric vulnerability in the emergency department (ED) have shown limited predictive power, especially in diverse populations. We investigated the relationship of a quick and easy-to-administer geriatric vulnerability scoring system with functional decline and mortality in older patients admitted to multiple hospitals through the ED in the United States (US) and Brazil (BR).

Method: Federated, international, multicenter observational study of hospitalized ED patients aged ≥ 65 from US and BR.

Machine-learning versus traditional methods for prediction of all-cause mortality after transcatheter aortic valve implantation: a systematic review and meta-analysis.

Background: Accurate mortality prediction following transcatheter aortic valve implantation (TAVI) is essential for mitigating risk, shared decision-making and periprocedural planning. Surgical risk models have demonstrated modest discriminative value for patients undergoing TAVI and are typically poorly calibrated, with incremental improvements seen in TAVI-specific models. Machine learning (ML) models offer an alternative risk stratification that may offer improved predictive accuracy.

Disparities in Rehabilitation Services for Victims of Violence.

Introduction: Access to rehabilitation services after a traumatic injury improves functional outcomes. No study has examined the association between injury intent, violent versus nonviolent, and receipt of rehabilitation services after injury.

Materials And Methods: We conducted a retrospective cohort study of injured adult patients admitted to our level I trauma center from January 1, 2014 to December 31, 2021.

Updating US Public Health For Healthier Communities.

The United States faces urgent public health challenges, including high preventable death rates, pervasive health disparities, and emerging health risks, despite unprecedented medical progress. This article, part of the National Academy of Medicine's Vital Directions for Health and Health Care: Priorities for 2025 initiative, presents a vision for modernizing the US public health system to address these twenty-first-century challenges through federally supported partnerships with health care, social services, and community organizations. We identify actions to address persistent public health challenges that stem from insufficient and fragmented funding models, inadequate data infrastructure, workforce vulnerabilities, and limited public trust.

Exploring Glypican-3 targeted CAR-NK treatment and potential therapy resistance in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer and the second leading cause of cancer-related mortality globally. Despite advancements in current HCC treatment, it remains a malignancy with poor prognosis. Therefore, developing novel treatment options for patients with HCC is urgently needed.

Disparities of women's authorship in Colombia: A cross-sectional analysis.

Accepted manuscripts published in medical journals play a crucial role within the scientific community. Over the past few decades, there has been a gradual increase in the number of women entering the medical field. However, women remain underrepresented as first and last authors in medical journals.

Hydrogen Tunneling and Conformational Motions in Nonadiabatic Proton-Coupled Electron Transfer between Interfacial Tyrosines in Ribonucleotide Reductase.

Ribonucleotide reductase (RNR) is essential for DNA synthesis and repair in all living organisms. The mechanism of RNR requires long-range radical transport through a proton-coupled electron transfer (PCET) pathway spanning two different protein subunits. Herein, the direct PCET reaction between the interfacial tyrosine residues, Y356 and Y731, is investigated with a vibronically nonadiabatic theory that treats the transferring proton and all electrons quantum mechanically.